It is proposed to continue collaborative projects involving Epstein-Barr virus (EBV) specific serology heretofore supported by a contract. They are divided into two groups. I. Application of EBV-specific serologic tests to the diagnosis, prognosis and monitoring of patients with Burkitt's lymphoma (BL) and nasopharyngeal carcinoma (NPC). These studies have the aim to determine whether observations made in endemic regions of BL and NPC hold also for sporadic cases elsewhere in the world, and to apply them to the management of patients. BL and NPC evoke antibody spectra of several immune globulin classes to a number of EBV-coded antigens which are characteristic for each and thus should facilitate their diagnosis. Projects on juvenile and adult NPC in the United States, including Alaskan natives, are intended to demonstrate the value of EBV-specific diagnostic tests particularly in cases of cervical lymph node metastasee from occult primary carcinomas and to confirm that following initially effective therapy recurrent tumors are heralded by rising antibody titers months prior to their clinical detection, whereas lasting therapeutic success becomes evident from steadily declining IgG and IgA antibody titers to viral capsid antigen and the diffuse component of the early antigens. Also patients with B cell lymphomas arising at enhanced frequency in immunodeficient patients, now shown to be EBV-associated, will be studied serially for EBV-specific antibody responses when found in the second group of projects. II. Humoral and cellular immune responses to primary and persistent infections of individuals with immune deficiencies, whether genetically transmitted (e.g. ataxiatelangiectasia), therapeutically induced (e.g. renal transplant recipient), or evoked by lymphoproliferative malignancies (e.g. Hodgkin's disease). These projects have the aim to relate elevated anti-VCA and anti-EA titers and/or loss of antibodies to EBV nuclear antigen, measured in this laboratory, to absence or dysfunction of given subsets of leukocytes determined in Dr. George Klein's laboratory. These studies should provide information on the cellular immune reactions responsible for self-limitation of primary EBV infections or control of the regularly ensuing persistent viral carrier state and when absent, permit escape of EBV-transformed cells from immunosurviellance.